DOCSLIB.ORG

The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection 1521-009X/46/8/1212–1225$35.00 https://doi.org/10.1124/dmd.117.079038 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:1212–1225, August 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Minireview The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection Kimberly L. Garrison, Polina German, Erik Mogalian, and Anita Mathias Gilead Sciences Inc., Foster City, California Received October 18, 2017; accepted March 26, 2018 ABSTRACT Downloaded from Several safe and highly effective direct-acting antiviral (DAA) drugs plus dasabuvir with or without ribavirin), the potential for drug-drug for chronic hepatitis C virus (HCV) have been developed and greatly interactions (DDIs) becomes an important consideration for HCV- increase the number of therapeutic options available to successfully infected individuals with comorbidities that require concomi- treat HCV infection. However, because treatment regimens contain tant medications, such as human immunodeficiency virus/HCV at least two drugs (e.g., elbasvir and grazoprevir, glecaprevir and coinfection or immunosuppression after liver transplantation. This pibrentasvir, or sofosbuvir with daclatasvir, simeprevir, ledipasvir, or review details the pharmacokinetics and DDI potential of approved dmd.aspetjournals.org velpatasvir) and up to five drugs (ombitasvir/paritaprevir/ritonavir DAAs for the treatment of HCV infection. Introduction medications were associated with frequent adverse effects and in- Chronic hepatitis C virus (HCV) is a global health problem affecting an adequate antiviral efficacy (assessed as sustained virologic response). In 2013, the U.S. Food and Drug Administration approved the first direct- estimated 71 million people worldwide (http://www.who.int/mediacentre/ at ASPET Journals on September 28, 2021 factsheets/fs164/en/). In the United States, an estimated 2.7–3.9 million acting antiviral (DAA) protease inhibitors, boceprevir and telaprevir. people have chronic HCV infection, which causes more than 19,000 When administered with Peg-IFN plus ribavirin, boceprevir- and deaths annually http://www.euro.who.int/en/health-topics/communi- telaprevir-containing regimens resulted in higher sustained virologic cable-diseases/hepatitis/data-and-statistics, although under-reporting response rates compared with Peg-IFN plus ribavirin monotherapy, but may contribute to an underestimation by up to 5-fold (Mahajan et al., the safety and efficacy of these regimens remained suboptimal. Since 2014). In the European Region, approximately 15 million people have then, many highly effective and well tolerated DAA regimens have been chronic HCV infection, which results in 86,000 deaths annually in WHO developed, consisting of various combinations of nucleotide analog European Member States. (http://www.who.int/mediacentre/factsheets/ NS5B inhibitors, non-nucleotide NS5B inhibitors, NS5A inhibitors, fs164/en/). After acute infection with HCV, approximately 75%–85% of and/or NS3/4A protease inhibitors, including simeprevir, daclatasvir, individuals fail to spontaneously clear the virus and thus progress to sofosbuvir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir plus chronic infection. Complications of chronic HCV infection include liver dasabuvir, sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ cirrhosis, end-stage liver disease, and hepatocellular carcinoma; in the velpatasvir/voxilaprevir, and glecaprevir/pibrentasvir. The combination United States, HCV remains one of the leading indications for liver therapies now achieve cure rates approaching 100%, and regimens have transplantation (Kim et al., 2017). Almost three-quarters of the reported even become available for those patients who fail the available, highly HCV-related deaths in the United States have occurred in the baby effective DAA regimens (Vosevi, 2017a,b). boomer generation, with a median age at death (57 years) that is Given the significant and rapid advancements in highly effective approximately 20 years less than the average lifespan for the general treatment options, boceprevir and telaprevir (which are no longer population (Smith et al., 2012). available commercially) and asunaprevir (an NS3 protease inhibitor, Prior to 2011, the standard of care for treating HCV included which is only approved for use in China and Japan) will not be further administration of pegylated-interferon (Peg-IFN) and ribavirin. These discussed in this article. The availability of highly effective and well tolerated DAA regimens The work was supported by Gilead Sciences Inc. represents a significant advancement for patients with chronic HCV https://doi.org/10.1124/dmd.117.079038. infection; however, the potential for metabolic or transport-mediated ABBREVIATIONS: 3TC, lamivudine; ABC, abacavir; ALT, alanine aminotransferase; ARV, antiretroviral; ATV, atazanavir; AUC, area under the plasma concentration versus time curve; BCRP, breast cancer resistance protein; COBI, cobicistat; DAA, direct-acting antiviral; DDI, drug-drug interaction; DRV, darunavir; DTG, dolutegravir; EE, ethinyl estradiol; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; GS-331007, 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)pyrimidine-2,4-dione; HCV, hepatitis C virus; HIV, human immunodeficiency virus; LPV, lopinavir; MRP, multidrug resistance protein; NRTI, nucleoside or nucleotide reverse transcriptase inhibitor; OATP, organic anion-transporting polypeptide; P-gp, p-glycoprotein; P450, cytochrome P450; Peg-IFN, pegylated-interferon; RAL, raltegravir; RPV, rilpivirine; SmPC, European Summary of Product Characteristics; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TFV, tenofovir; UGT, uridine glucuronosyltransferase; USPI, U.S. Prescribing Information. 1212 The DDI Potential of HCV DAAs 1213 drug-drug interactions (DDIs) warrants consideration because these genotype 1, 4, 5, or 6 infection. Ledipasvir/sofosbuvir is administered treatment regimens contain at least two drugs (e.g., ledipasvir/sofosbuvir) once daily without regard to food (Harvoni, 2017a,b). Ledipasvir is and up to five drugs (ombitasvir/paritaprevir/ritonavir plus dasabuvir primarily excreted unchanged in bile, with ,1% excreted in urine plus ribavirin). Careful thought about possible DDIs is especially (Kirby et al., 2013). Ledipasvir is both a substrate and an inhibitor of important for patients with chronic conditions such as human P-gp/BCRP; ledipasvir does not inhibit or induce cytochrome P450 immunodeficiency virus (HIV)/HCV coinfection, individuals who (P450) enzymes or uridine glucuronosyltransferases (UGTs) (German receive immunosuppressive therapy after liver transplantation, or et al., 2014b). patients with other comorbidities that require concomitant medication. This review details the pharmacokinetics and DDI potential of currently Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir approved DAAs for the treatment of HCV infection. The combination of ombitasvir (25 mg), an NS5A inhibitor, with a ritonavir (100 mg)–boosted NS3/4A protease inhibitor, paritaprevir Summary of DAA Characteristics (150 mg), plus a non-nucleotide NS5B inhibitor, dasabuvir (150 mg twice daily), with or without ribavirin (with food) is approved for Below is a list of DAAs available as single agents (to be used in treatment of HCV genotype 1 infection (Viekira Pak, 2017; Viekirax, combination with other DAAs) or as complete treatment regimens. 2018). Ombitasvir/paritaprevir/ritonavir is also approved for use with Table 1 summarizes clinical and/or nonclinical data characterizing ribavirin against HCV genotype 4 (Technivie, 2016; Viekirax, 2018). DAAs as substrates, inducers, or inhibitors of metabolic enzymes and Ombitasvir, ritonavir, paritaprevir, and dasabuvir are primarily elimi- Downloaded from transporters. nated in the feces, whereas 1.91%, 8.8%, 11.3%, and approximately 2% of the doses are excreted in the urine, respectively (Viekira Pak, 2017; Simeprevir Viekirax, 2018). Ombitasvir is primarily excreted unchanged, whereas Simeprevir (150 mg), an NS3/4A protease inhibitor, is administered paritaprevir, ritonavir, and dasabuvir are primarily metabolized. Ombi- once daily in combination with sofosbuvir or Peg-IFN plus ribavirin in tasvir is a substrate of amidases, CYP3A, and P-gp/BCRP. Paritaprevir subjects with HCV genotype 1 infection (Olysio, 2017). Simeprevir is is a substrate for CYP3A, P-gp/BCRP, and OATP1B1/3. Dasabuvir dmd.aspetjournals.org dosed with food because food increases its bioavailability [area under the is a substrate for CYP2C8 and P-gp/BCRP (Menon et al., 2015). plasma concentration versus time curve (AUC)] by 61%–69% (Olysio, Ombitasvir, paritaprevir, and dasabuvir all inhibit UGT1A1 (Viekira 2016, 2017). Simeprevir is primarily eliminated in the feces (91%) Pak, 2017). In addition, paritaprevir inhibits BCRP and OATP1B1/3, predominantly as metabolites, with ,1% excreted in the urine. and dasabuvir inhibits BCRP (Viekira Pak, 2017). To increase its Simeprevir is a substrate of CYP3A, P-glycoprotein (P-gp)/breast cancer systemic exposure, paritaprevir is coadministered with low-dose resistance protein (BCRP), multidrug resistance protein MRP2, and ritonavir (Norvir, 2017). organic anion-transporting polypeptide OATP1B1/3 and inhibits CYP1A2, CYP3A4 (intestinal), P-gp, and OATP1B1/3 (Ouwerkerk- Sofosbuvir/Velpatasvir at ASPET Journals on September 28, 2021 Mahadevan et al., 2016; Olysio, 2017). Velpatasvir
Load more

Recommended publications
  • Avis De La Commission De La Transparence
    COMMISSION DE LA TRANSPARENCE Avis 6 décembre 2017 Date d’examen par la Commission : 22 novembre 2017 glécaprévir / pibrentasvir MAVIRET 100 mg/40 mg, comprimé pelliculé B/ 84 (CIP 34009 301 087 6 5) Laboratoire ABBVIE Code ATC Code ATC non encore attribué (association d’antiviraux à action directe) Motif de l’examen Inscription Sécurité Sociale (CSS L.162-17) Listes concernées Collectivités (CSP L.5123-2) Indications « Traitement de l’infection chronique par le virus de l’hépatite C (VHC) de concernées génotypes 1 à 6 chez les adultes » HAS - Direction de l'Evaluation Médicale, Economique et de Santé Publique 1/28 Avis 2 SMR Important Compte tenu de : - son efficacité virologique pangénotypique importante (>90%), avec une durée de traitement de 8 à 12 semaines pour la majorité des patients sans cirrhose ou avec cirrhose compensée (Child-Pugh A uniquement), - la démonstration d’une efficacité importante dans des populations particulières telles que les patients insuffisants rénaux ou hémodialysés pour lesquelles les alternatives sont limitées, - son profil de tolérance et de résistance satisfaisant mais avec un ASMR potentiel d’interactions médicamenteuses important, - l’existence d’alternatives qui permettent également un traitement court (8 à 12 semaines) sans adjonction de ribavirine, la Commission considère que la spécialité, apporte, au même titre que les autres combinaisons d’antiviraux d’action directe disponibles (EPCLUSA, HARVONI, VIEKIRAX, EXVIERA, ZEPATIER), une amélioration du service médicale rendue mineure (ASMR IV) dans
    [Show full text]
  • SPIRONOLACTONE Spironolactone – Oral (Common Brand Name
    SPIRONOLACTONE Spironolactone – oral (common brand name: Aldactone) Uses: Spironolactone is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat swelling (edema) caused by certain conditions (e.g., congestive heart failure) by removing excess fluid and improving symptoms such as breathing problems. This medication is also used to treat low potassium levels and conditions in which the body is making too much of a natural chemical (aldosterone). Spironolactone is known as a “water pill” (potassium-sparing diuretic). Other uses: This medication has also been used to treat acne in women, female pattern hair loss, and excessive hair growth (hirsutism), especially in women with polycystic ovary disease. Side effects: Drowsiness, lightheadedness, stomach upset, diarrhea, nausea, vomiting, or headache may occur. To minimize lightheadedness, get up slowly when rising from a seated or lying position. If any of these effects persist or worsen, notify your doctor promptly. Tell your doctor immediately if any of these unlikely but serious side effects occur; dizziness, increased thirst, change in the amount of urine, mental/mood chances, unusual fatigue/weakness, muscle spasms, menstrual period changes, sexual function problems. This medication may lead to high levels of potassium, especially in patients with kidney problems. If not treated, very high potassium levels can be fatal. Tell your doctor immediately if you notice any of the following unlikely but serious side effects: slow/irregular heartbeat, muscle weakness. Precautions: Before taking spironolactone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.
    [Show full text]
  • Daklinza, INN-Daclatasvir
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Daklinza 30 mg film-coated tablets Daklinza 60 mg film-coated tablets Daklinza 90 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Daklinza 30 mg film-coated tablets Each film-coated tablet contains daclatasvir dihydrochloride equivalent to 30 mg daclatasvir. Daklinza 60 mg film-coated tablets Each film-coated tablet contains daclatasvir dihydrochloride equivalent to 60 mg daclatasvir. Daklinza 90 mg film-coated tablets Each film-coated tablet contains daclatasvir dihydrochloride equivalent to 90 mg daclatasvir. Excipient(s) with known effect Each 30-mg film-coated tablet contains 58 mg of lactose (as anhydrous). Each 60-mg film-coated tablet contains 116 mg of lactose (as anhydrous). Each 90-mg film-coated tablet contains 173 mg of lactose (as anhydrous). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet). Daklinza 30 mg film-coated tablets Green biconvex pentagonal of dimensions 7.2 mm x 7.0 mm, debossed tablet with "BMS" on one side and "213" on the other side. Daklinza 60 mg film-coated tablets Light green biconvex pentagonal of dimensions 9.1 mm x 8.9 mm, debossed tablet with "BMS" on one side and "215" on the other side. Daklinza 90 mg film-coated tablets Light green biconvex round of dimension 10.16 mm diameter, embossed tablet with "BMS" on one side and "011" on the other side.
    [Show full text]
  • Sofosbuvir for the Treatment of Genotype 1 Hepatitis C in Subjects Aged 65 Years Or Older
    AMERICAN ASSOCIATION FOR THE STUDY OFLIVERD I S E ASES HEPATOLOGY, VOL. 63, NO. 4, 2016 Safety and Efficacy of Ledipasvir/ Sofosbuvir for the Treatment of Genotype 1 Hepatitis C in Subjects Aged 65 Years or Older Sammy Saab,1 Sarah H. Park,1 Masashi Mizokami,2 Masao Omata,3 Alessandra Mangia,4 Ed Eggleton,5 Yanni Zhu,5 Steven J. Knox,5 Phil Pang,5 Mani Subramanian,5 Kris Kowdley,6 and Nezam H. Afdhal7 Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus 65 years among subjects enrolled in phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment-emergent adverse events (AEs), and graded laboratory abnor- malities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were 65 years of age, of whom 24 were aged 75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/ 2029) of subjects aged <65 years and 98% (258/264) of subjects aged 65 years. The most common AEs in both LDV/ SOF groups that occurred in 10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts.
    [Show full text]
  • KALETRA (Lopinavir/Ritonavir)
    HIGHLIGHTS OF PRESCRIBING INFORMATION CONTRAINDICATIONS These highlights do not include all the information needed to use • Hypersensitivity to KALETRA (e.g., toxic epidermal necrolysis, Stevens- KALETRA safely and effectively. See full prescribing information for Johnson syndrome, erythema multiforme, urticaria, angioedema) or any of KALETRA. its ingredients, including ritonavir. (4) • Co-administration with drugs highly dependent on CYP3A for clearance KALETRA (lopinavir and ritonavir) tablet, for oral use and for which elevated plasma levels may result in serious and/or life- KALETRA (lopinavir and ritonavir) oral solution threatening events. (4) Initial U.S. Approval: 2000 • Co-administration with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for RECENT MAJOR CHANGES loss of virologic response and possible resistance and cross resistance. (4) Contraindications (4) 12/2019 WARNINGS AND PRECAUTIONS The following have been observed in patients receiving KALETRA: INDICATIONS AND USAGE • The concomitant use of KALETRA and certain other drugs may result in KALETRA is an HIV-1 protease inhibitor indicated in combination with other known or potentially significant drug interactions. Consult the full antiretroviral agents for the treatment of HIV-1 infection in adults and prescribing information prior to and during treatment for potential drug pediatric patients (14 days and older). (1) interactions. (5.1, 7.3) • Toxicity in preterm neonates: KALETRA oral solution should not be used DOSAGE AND ADMINISTRATION in preterm neonates in the immediate postnatal period because of possible Tablets: May be taken with or without food, swallowed whole and not toxicities. A safe and effective dose of KALETRA oral solution in this chewed, broken, or crushed.
    [Show full text]
  • Ombitasvir, Paritaprevir/Ritonavir (Technivie )
    Ombitasvir, paritaprevir/ritonavir (Technivie®) National Abbreviated Review Drug Monograph December 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, VISN Pharmacist Executives and Office of Public Health The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information1 Description/ Technivie is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. Mechanism of Action Ritonavir does not have activity against Hepatitis C virus (HCV); it is included in the regimen as a pharmacokinetic enhancer (i.e. increase concentration of paritaprevir). The other two agents are direct-acting antivirals with different mechanisms of action. Ombitasvir is a NS5A inhibitor and paritaprevir is a NS3/4A protease inhibitor. Indication(s) under Review in Fixed-dose combination of ombitasvir, paritaprevir and ritonavir with ribavirin this document is indicated for the treatment of chronic hepatitis C genotype 4 infections in adults without cirrhosis. NOTE: Per prescribing information, this combination may be administered without ribavirin in treatment-naïve patients who cannot tolerate ribavirin Dosage Form(s) Under Ombitasvir, paritaprevir, ritonavir 12.5/75/50mg tablet Review REMS NO REMS Pregnancy Rating Pregnancy Category B; however, when ribavirin is co-administered, then regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Executive Summary1-2 Efficacy The FDA approval of ombitasvir, paritaprevir and ritonavir with ribavirin was primarily based on one phase 2b randomized, open-label, multi-center trial (called PEARL-1).
    [Show full text]
  • Sofosbuvir/Ledipasvir for HIV •
    Hepatitis C: Drugs and Combinations Melissa Osborn MD Associate Professor MetroHealth Medical Center Case Western Reserve University Cleveland, OH Faculty and Planning Committee Disclosures Please consult your program book. Off-Label Disclosure The following off-label/investigational uses will be discussed in this presentation: • Sofosbuvir/ledipasvir for HIV •. Investigational agents for hepatitis C will be mentioned – Asunaprevir – Daclatasvir – Beclabuvir – Grazoprevir – Elbasvir – GS-5816 Learning Objectives Upon completion of this presentation, learners should be better able to: • apply clinical trial data on new hepatitis C therapies to their patient population. • select which new hepatitis C therapies are appropriate to use with common antiretrovirals. Evolution of interferon-based therapy in HCV-monoinfected genotype 1 patients Sustained Virologic Response 100% 90% 80% 80% 75% 67% 60% 42% 46% 40% 28% 20% 7% 0% Std interferon-alfa IFN + RBV Peg-alfa-2b+RBV Peg-alfa-2a +RBV P/R/Telaprevir P/R/Boceprevir P/R/Simeprevir P/R/Sofosbuvir McHutchison, NEJM 1998; 339: 1485-92 Jacobson, NEJM 2011; 364:2405-16 Fried, NEJM 2002; 347: 975-82 Poordad, NEJM 2011; 364: 1195-206 Manns, Lancet 2001; 358:958-65 Jacobson, AASLD 2013 #1122 Lawitz, NEJM 2013 Evolution of HCV Therapy: Genotype 1 Patients Naïve to Therapy: HIV-HCV coinfection Sustained Virologic Response 80% 75% 74% 67% 61% 60% 46% 42% 40% 28% 29% 20% 17% 7% 7% 0% Std interferon-alfa IFN + RBV Peg-alfa-2b+RBV Peg-alfa-2a +RBV P/R/Telaprevir P/R/Boceprevir Torriani, NEJM, 2004 351:438-50
    [Show full text]
  • Hepatitis C Agents Therapeutic Class Review
    Hepatitis C Agents Therapeutic Class Review (TCR) November 2, 2018 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004–2018 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS Drug Mfr FDA-Approved Indications Interferons peginterferon alfa-2a Genentech Chronic hepatitis C (CHC) 1 (Pegasys®) .
    [Show full text]
  • Acid Reducing Agent Treatment Selector
    www.hep-druginteractions.org Acid Reducing Agent Treatment Selector Charts produced April 2018. Full information available at www.hep-druginteractions.org For personal use only. Not for distribution. For personal use only. Not for distribution. For personal use only. Not for distribution. For personal use only. Not for distribution. DCV EBR/GZR GLP/PIB LED/SOF OBV/PTV/r OBV/PTV/r +DSV SMV SOF SOF/VEL SOF/VEL/VOX Aluminium hydroxide ↔ ↔ ↔ a ↔ ↔ ↔ ↔ b a a Antacids ↔ ↔ ↔ a ↔ ↔ ↔ ↔ b a a d d d Cimetidine ↔ ↔ ↔ ↔ ↔ Famotidine 18% c e ↔ ↔ ↔ ↔ f ↔ g H2 RA Ranitidine ↔ ↔ d ↔ ↔ ↔ ↔ d d Esomeprazole ↔ ↔ i k ↓ ↓ ↔ ↔ m o Lansoprazole ↔ ↔ i k ↓ ↓ ↔ ↔ m o Omeprazole 16% ↔ j l ↓ 54% ↓ 38% ↑ 21% ↔ n p PPI Pantoprazole ↔ h i k ↓ ↓ ↔ ↔ m o Rabeprazole ↔ ↔ i k ↓ ↓ ↔ ↔ m p Colour Legend No clinically significant interaction expected. These drugs should not be coadministered. Potential interaction which may require a dosage adjustment or close monitoring. Potential interaction predicted to be of weak intensity. Text Legend ↑ Potential increased exposure of the acid reducing agent Potential increased exposure of HCV DAA ↓ Potential decreased exposure of the acid reducing agent Potential decreased exposure of HCV DAA ↔ No significant effect Numbers refer to increased or decreased AUC as observed in drug-drug interaction studies. H2 RA H2 receptor antagonists PPI Proton pump inhibitors a It is recommended to separate administration of the acid reducing agent and the DAA by 4 hours. b Consider separating administration of the acid reducing agent and sofosbuvir by 2 hours. c Elbasvir AUC increased by 5%; grazoprevir AUC increased by 10%. d H2 receptor antagonists at a dose that does not exceed doses comparable to famotidine 40 mg twice daily can be given simultaneously with or 12 hours apart from the DAA.
    [Show full text]
  • Sofosbuvir-Based and Elbasvir/Grazoprevir Treatment Fai
    Sofosbuvir-Based and Elbasvir/Grazoprevir Treatment Fai... From www.HCVGuidance.org on September 27, 2021 Sofosbuvir-Based and Elbasvir/Grazoprevir Treatment Failures In general, persons who have experienced treatment failure with a sofosbuvir-based regimen should be retreated with 12 weeks of sofosbuvir/velpatasvir/voxilaprevir. The main exception is persons with genotype 3 and cirrhosis, in whom addition of ribavirin to sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is recommended. Sixteen weeks of glecaprevir/pibrentasvir is an alternative regimen. Elbasvir/grazoprevir treatment failure patients should also be retreated with 12 weeks of sofosbuvir/velpatasvir/voxilaprevir. However, glecaprevir/pibrentasvir for 16 weeks is not recommended as an alternative for this group of patients. Recommended and alternative regimens listed by evidence level and alphabetically for: Sofosbuvir-Based Treatment Failures, With or Without Compensated Cirrhosisa RECOMMENDED DURATION RATING Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 12 weeks I, A mg)/voxilaprevir (100 mg)b ALTERNATIVE DURATION RATING Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) 16 weeks I, A except for NS3/4 protease inhibitor inclusive combination DAA regimen failuresc Not recommended for genotype 3 infection with sofosbuvir/NS5A inhibitor experience. a For decompensated cirrhosis, please refer to the appropriate section. b Genotype 3: Add weight-based ribavirin if cirrhosis is present and there are no contraindications. c This regimen is not recommended for patients with prior exposure to an NS5A inhibitor plus NS3/4 PI regimens (eg. Elbasvir/grazoprevir). Recommended Regimen Sofosbuvir/Velpatasvir/Voxilaprevir The placebo-controlled, phase 3 POLARIS-1 trial evaluated a 12-week course of the daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) in 263 persons with a prior NS5A inhibitor-containing DAA regimen failure.
    [Show full text]
  • Hepatitis C Treatment
    Hepatitis C Treatment The goal of treatment for hepatitis C virus (HCV) is to cure the virus, which can be done with a combination of drugs. The specific meds used and the duration of treatment depend on a number of factors, including HCV genotype (genetic structure of the virus), viral load, past treatment experience, degree of liver damage, ability to tolerate the prescribed treatment, and whether the person is waiting for a liver transplant or is a transplant recipient. In some cases, HCV treatment may be limited by your health insurance plan or drug formulary. Here’s information about each type, or class, of approved HCV treatment along with drugs in the late stages of development: Multi-Class Combination Drugs Brand Name Generic Name Status Pharmaceutical Company Epclusa* sofosbuvir + velpatasvir Approved Gilead Sciences Harvoni* ledipasvir + sofosbuvir Approved Gilead Sciences Mavyret glecaprevir + pibrentasvir Approved AbbVie Vosevi sofosbuvir/velpatasvir/ Approved Gilead Sciences voxilaprevir Zepatier elbasvir + grazoprevir Approved Merck n/a daclatasvir + asunaprevir + Phase III Bristol-Myers Squibb beclabuvir *generic available What are they? Multi-class combination drugs are a combination of drugs formulated into a single pill or package of pills. For instance, the drug Harvoni combines two drugs, ledipasvir and sofosbuvir. Ledipasvir is an NS5A inhibitor and is only sold as part of Harvoni; sofosbuvir may be prescribed separately under the brand name of Sovaldi. Pegylated Interferon Alfa Brand Name Generic Name Status Pharmaceutical Company Pegasys peginterferon alfa-2a Approved Genentech What are they? Interferon is a protein made by the immune system, named because it interferes with viral reproduction. In addition, interferon signals the immune system to recognize and respond to microorganisms, including viral and bacterial infections.
    [Show full text]
  • Effectiveness and Safety of Sofosbuvir/Velpatasvir ± Ribavirin Vs
    Original research Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-002060 on 7 February 2020. Downloaded from Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients Luis Margusino- Framiñán,1,2 Purificación Cid- Silva,1,2 Sandra Rotea- Salvo,1 Álvaro Mena- de- Cea,2,3 Francisco Suárez- López,4 Pilar Vázquez- Rodríguez,2,3 Manuel Delgado- Blanco,2,4 Ana Isabel Sanclaudio- Luhia,5 Isabel Martín- Herranz,1 Ángeles Castro- Iglesias2,3 1Pharmacy Service, Universitary ABSTRact 1.1%, with a total affected population of 5.6 million Hospital of A Coruña, A Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/ people.1 The prevalence of HCV genotypes varies Coruña, Spain 2 among regions, with genotype 3 (G3) being the Division of Clinical Virology, VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are Biomedical Research Institute the drug combinations of choice for treating individuals second most prevalent in Europe after genotype 1 of A Coruña (INIBIC), with genotype 3 hepatitis C virus (G3- HCV) infection. The (G1), accounting for approximately 25% of cases Universitary Hospital of A objective of this study was to evaluate the effectiveness of chronic hepatitis C (CHC).2 Compared with Coruña (CHUAC), Sergas, and safety of SOF/VEL±RBV compared with GLE/PIB for G1- HCV, G3- HCV chronic infection has a faster University of A Coruña (UDC), 3–6 A Coruña, Spain treating G3- HCV infection under routine clinical practice progression to liver cirrhosis and hepatocellular
    [Show full text]